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Trial record 1 of 1 for:    al3818-us-004
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A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma (APROMISS)

This study is currently recruiting participants.
Verified September 2017 by Advenchen Laboratories, LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT03016819
First Posted: January 11, 2017
Last Update Posted: September 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Advenchen Laboratories, LLC
  Purpose
This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Condition Intervention Phase
Alveolar Soft Part Sarcoma Leiomyosarcoma Synovial Sarcoma Soft-Tissue Sarcoma Drug: AL 3818 Drug: Dacarbazine Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Study of AL3818 (Anlotinib) Hydrochloride Monotherapy in Subjects With Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

Resource links provided by NLM:


Further study details as provided by Advenchen Laboratories, LLC:

Primary Outcome Measures:
  • Objective Response Rate (ORR) (ASPS) [ Time Frame: Up to 48 months ]
    To determine ORR in subjects with ASPS, defined as percentage of subjects who achieve a Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1 as evaluated by a blinded independent radiological review (BICR).

  • Progression Free Survival (PFS) (LMS/SS) [ Time Frame: From time of randomization to the date of disease progression or death from any cause, up to 48 months ]
    To compare PFS in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined a median number of months from the date of randomization until the first documented sign of disease progression or death due to any causes, whichever occurs earlier as evaluated by a blinded independent radiologic review (BICR).


Secondary Outcome Measures:
  • Duration of Response (DOR) (ASPS) [ Time Frame: Up to 48 months ]
    To determine DOR in subjects with ASPS, defined as median number of months from date of first documented objective response until first documented sign of disease progression or death due to any causes

  • Objective Response Rate (ORR) (LMS/SS) [ Time Frame: Up to 48 months ]
    To compare ORR in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined as percentage of subjects who achieve a Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1 as evaluated by a blinded independent radiological review (BICR).


Estimated Enrollment: 219
Actual Study Start Date: August 15, 2017
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indication A: ASPS AL3818 Arm
All subjects with ASPS will be assigned to the open-label AL3818 arm to receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Drug: AL 3818
Anlotinib (AL3818) 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)
Other Name: Anlotinib
Experimental: Indication B: LMS AL3818 Arm
Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Drug: AL 3818
Anlotinib (AL3818) 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)
Other Name: Anlotinib
Active Comparator: Indication B: LMS Dacarbazine Arm
Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle.
Drug: Dacarbazine
Dacarbazine 1000 mg/m2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle
Other Name: DTIC
Experimental: Indication C: SS AL3818 Arm
Subjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Drug: AL 3818
Anlotinib (AL3818) 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)
Other Name: Anlotinib
Active Comparator: Indication C: SS Dacarbazine Arm
Subjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle.
Drug: Dacarbazine
Dacarbazine 1000 mg/m2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle
Other Name: DTIC

Detailed Description:

APROMISS is a phase 3 study evaluating the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). Population pharmacokinetics and exploratory exposure-response analyses will also be conducted in subjects receiving AL3818.

Indication A: 56 subjects with metastatic or advanced ASPS not amenable to surgical resection will receive open-label AL3818 at a dose of 12 mg once daily in 21-day cycles (14 days on treatment, 7 days off treatment) until disease progression (defined by RECIST version 1.1) ot unacceptable toxicity. The primary endpoint is objective response rate (ORR), secondary endpoint is duration of response (DOR).

Indication B: 68 subjects with metastatic or advanced LMS who have failed at least one prior line of approved therapy will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR).

Indication C: 95 subjects with with metastatic or advanced SS who have failed at least one prior line of approved therapy, including first-line anthracycline-containing chemotherapy, will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR).

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent provided before any study-specific procedures are initiated. Subject must be able to understand and be willing to sign a written informed consent form.
  2. Male or female at least 18 years of age.
  3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma.

    • Indication B - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone).
    • Indication C - SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma.
  4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

    • Indications B - LMS: Subjects previously treated with at least one prior line of approved therapy.
    • Indication C - SS: Subjects previously treated with at least one prior line of approved therapy, including first-line anthracycline containing regimen.
  5. Show objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability (excluding ASPS subjects who have not received prior therapy) within 6 months of enrollment.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.
  8. Life expectancy of at least 3 months.
  9. Females of childbearing potential must have a negative pregnancy test (by serum beta-HCG) within 7 days prior to the start of treatment.
  10. Female of childbearing potential must be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the investigator), or agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 2 years. - Males must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) at the discretion of the investigator.
  11. Adequate hematologic, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

    • Total bilirubin < the upper limit of normal (ULN)
    • Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x of ULN for subjects with liver involvement of their cancer)
    • Amylase and lipase < 1.5 x of ULN
    • Serum creatinine < 1.5 x of ULN
    • Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min (Cockcroft and Gault)
    • International normalize ratio (INR) and the partial thromboplastin time (PTT) < 1.5 x ULN. (Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of an underlying abnormality in coagulation parameters exists)
    • Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil count > 1,500 cells/mm3
    • Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver involvement of their cancer)
    • Spot urine must not show 1+ or more protein in urine or the subject will require a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion <1,000 mg per 24 hours.
  12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

  1. Prior treatment with or have known hypersensitivity to AL3818.
  2. a. Indication A - ASPS: Prior treatment with cediranib.

    • b. Indication B- LMS: Prior treatment with or have known hypersensitivity to dacarbazine.
    • c. Indication C - SS: Prior treatment with or have known hypersensitivity to dacarbazine.
  3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS, LS, or SS within 5 years before enrollment except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and T1).
  4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with any investigational product within 28 days of enrollment.
  5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or prior treatment with extended-field radiotherapy for evaluating tumor lesions within 14 days prior to enrollment.
  6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided that they are stable with no evidence of progression by imaging, and all neurologic symptoms have returned to baseline, and should not be using corticosteroids for at least 7 days prior to study treatment.
  7. Cavitary tumors or tumors invading or abutting large blood vessels.
  8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess within 6 months of enrollment.
  9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).
  10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and hemoptysis within 6 months prior to enrollment.
  11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of bleeding within 28 days prior to enrollment.
  12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial thrombosis) within 6 months prior to enrollment.
  13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided that INR or aPTT are within therapeutic limits (according to the medical standard of the enrollment institution) and patient has been on a stable dose of anticoagulants for at least two weeks prior to the first dose of study treatment.
  14. Serious non-healing wound, active ulcer, or unhealed bone fracture.
  15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment.
  16. CTCAE version 4.03 > grade 3 peripheral neuropathy
  17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any previous therapy (excluding alopecia and neurotoxicity < grade 2)
  18. QTc > 470 msec on electrocardiogram
  19. Severe and uncontrolled disease, including:

    • a. Class I and above myocardial ischemia or myocardial infarction, cardiac arrhythmia and Class 2 or above congestive heart failure classified according to New York Heart Association (NYHA)
    • b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mmHg despite optimal medical management)
    • c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2 infections)
    • d. Liver disease such as cirrhosis of the liver, decompensated liver disease, chronic active hepatitis needing anti-viral therapy
    • e. Renal failure needing hemodialysis or peritoneal dialysis
    • f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)
    • g. Untreated and uncontrolled epileptic seizures
    • h. History of psychotropic drug abuse and inability to quit
    • i. Untreated psychiatric disorders
  20. Known HIV-positive
  21. Had organ transplantation
  22. Clinical conditions affecting the intake and use of oral medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction)
  23. Females who are pregnant or are breast-feeding.
  24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5 or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there was an emergent or life-threatening medical condition that required it.
  25. Any medical intervention, condition or any other circumstance which in the opinion of the investigator or the sponsor's medical monitor, could compromise adherence to study procedures or study objectives.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03016819


Contacts
Contact: Melissa Chen 8055301550 melissac@advenchen.com
Contact: Judy Chen 8055301550 judyc@advenchen.com

Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90404
Contact: Steven Study Coordinator       SMSinger@mednet.ucla.edu   
Principal Investigator: Bartosz Chmielowski, MD, PhD         
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Lizbeth Study Coordinator       lizbeth.bornote@med.miami.edu   
Contact: Michelle Study Coordinator       mliendo@med.miami.edu   
Principal Investigator: Breelyn Wilky, MD         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Paige Study Coordinator       crawforp@med.umich.edu   
Principal Investigator: Rashmi Chugh, MD         
Sponsors and Collaborators
Advenchen Laboratories, LLC
  More Information

Responsible Party: Advenchen Laboratories, LLC
ClinicalTrials.gov Identifier: NCT03016819     History of Changes
Other Study ID Numbers: AL3818-US-004
First Submitted: January 6, 2017
First Posted: January 11, 2017
Last Update Posted: September 6, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Sarcoma
Leiomyosarcoma
Sarcoma, Synovial
Sarcoma, Alveolar Soft Part
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Neoplasms, Connective Tissue


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